AI & experimental-based discovery and preclinical IND-enabling studies of selective BMX inhibitors for development of cancer therapeutics.

The current work aims to design and provide a preliminary IND-enabling study of selective BMX inhibitors for cancer therapeutics development. BMX is an emerging target, more notably in oncological and immunological diseases. In this work, we have employed a predictive AI-based platform to design the selective inhibitors considering the novelty, IP prior protection, and drug-likeness properties.

Preparation and characterization of aqueous vitamin E/Soluplus dispersions for film coating applications.

Objective: The goals of this study were to (1) delineate a technique to prepare stable aqueous vitamin E/Soluplus dispersions; (2) characterize films cast from the aqueous dispersions; and (3) demonstrate the utility of the aqueous dispersions in fluid bed coating applications. This study demonstrated the feasibility of using vitamin E in the preparation of amphiphilic film withs potential use in delayed-release coating applications.

Methods: Low viscosity aqueous vitamin E/Soluplus dispersions were prepared by first spray drying ethanolic vitamin E/Soluplus solutions followed by high-shear homogenization of the solid dispersions in water.

Development and evaluation of paclitaxel nanoemulsion for cancer therapy.

Tocosol™ is a tocopherol-based paclitaxel (PTX) nanoemulsion consisting of α-tocopherol (α-T) isomer of vitamin E as a solubilizer and vitamin E TPGS as the primary emulsifier. Despite its positive attributes in early clinical studies, it failed the pivotal phase III clinical trials. The long-term goal of this work was to reformulate Tocosol™.

Development and in-vitro characterization of nanoemulsions loaded with paclitaxel/γ-tocotrienol lipid conjugates.

Vitamin E TPGS is a tocopherol (α-T) based nonionic surfactant that was used in the formulation of the Tocosol™ paclitaxel nanoemulsion, which was withdrawn from phase III clinical trials. Unlike tocopherols, however, the tocotrienol (T) isomers of vitamin E were found to have innate anticancer activity and were shown to potentiate the antitumor activity of paclitaxel. The primary objective of the present study was therefore to develop a paclitaxel nanoemulsions by substituting α-T oil core of Tocosol™ with γ-T in, and vitamin E TPGS with PEGylated γ-T as the shell, and test the nanoemulsions against Bx-PC-3 and PANC-1 pancreatic tumor cells.

Extraction of Vitamin E Isomers from Palm Oil: Methodology, Characterization, and Anti-Tumor Activity.

Vitamin E refers to a family of eight tocopherols (T) and tocotrienol (T3) isomers. Due to the unique pharmacological and anticancer activity of the individual isomers, there is a need to extract and separate the individual T3 isomers from T/T3 rich fractions of palm oil. The objective of the present study was to present a detailed protocol for the extraction of gram quantities of vitamin E isomers from a T3 rich fraction (Tocotrol™) that was obtained from palm oil, by column chromatography using a binary hexane:EtOAc (1-12%) phase system.

Gemcitabine-vitamin E conjugates: Synthesis, characterization, entrapment into nanoemulsions, and in-vitro deamination and antitumor activity.

Gemcitabine is the first line therapy for pancreatic cancer. It is, however, extensively metabolized to the inactive form by deamination enzymatic reaction. Conjugation of gemcitabine with fatty acids on its 4-amino group was found to protect it from deamination deactivation reaction.

Synthesis, physiochemical characterization, and in vitro antitumor activity of the amide and pH cleavable hydrazone conjugates of γ-tocotrienol isomer of vitamin E with methoxy-poly(ethylene) glycol.

The anticancer activity of water soluble methoxy polyethylene glycol (mPEG) derivatives of tocotrienol (T3) isomers of vitamin E was previously found to be reduced when compared to the parent free isomers. This could be due to the ester bond formation between the mPEG and the 6-OH group on the chroman moiety of the T3 isomer. To further investigate, the objectives of the current study were to (1) synthesize and characterize stable amide and cleavable hydrazone conjugates between mPEG and carbon-5 on the chroman moiety of T3, and (2) examine the cytotoxicity of the newly synthesized mPEG conjugates against breast (MCF-7 and MDA-MB-231) and pancreatic (BxPC-3 and PANC-1) cancer cells.

Synthesis, characterization, and in-vitro antitumor activity of the polyethylene glycol (350 and 1000) succinate derivatives of the tocopherol and tocotrienol isomers of Vitamin E.

Vitamin E refers to a group of saturated tocopherol (T) isomers and the biologically more active unsaturated tocotrienol (T) isomers. PEGylated α-tocopherol, commercially known as Vitamin E TPGS, has been used as an emulsifier and therapeutic agent for children with vitamin E deficiency. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers of vitamin E.

PEGylated γ-tocotrienol isomer of vitamin E: Synthesis, characterization, in vitro cytotoxicity, and oral bioavailability.

Vitamin E refers to a family of eight isomers divided into two subgroups, tocopherols and the therapeutically active tocotrienols (T3). The PEGylated α-tocopherol isomer of vitamin E (vitamin E TPGS) has been extensively investigated for its solubilizing capacity as a nonionic surfactant in various drug delivery systems. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers of vitamin E.

Effect of lipid viscosity and high-pressure homogenization on the physical stability of "Vitamin E" enriched emulsion.

Recently there has been a growing interest in vitamin E for its potential use in cancer therapy. The objective of this work was therefore to formulate a physically stable parenteral lipid emulsion to deliver higher doses of vitamin E than commonly used in commercial products. Specifically, the objectives were to study the effects of homogenization pressure, number of homogenizing cycles, viscosity of the oil phase, and oil content on the physical stability of emulsions fortified with high doses of vitamin E (up to 20% by weight).